Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial

Knop, Filip K.; Aroda, Vanita R.; Vale, Ronald D.; Holst-Hansen, Thomas; Laursen, Peter Nørkjær; Rosenstock, Julio; Rubino, Domenica; Garvey, W. Timothy

doi:10.1016/s0140-6736(23)01185-6

Cited by 129 publications

(35 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the OASIS-1 phase 3 trial, oral semaglutide 50 mg once daily showed weight losses of 15.1% after 68 weeks. 72 Also, orforglipron, an oral GLP-1 RA, has demonstrated weight losses of up to 14.7% after 36 weeks in the Phase 2 trial. 73 Thus, the efficacy of novel obesity pharmacotherapies is challenging the 25% weight losses that can be sustained on average after bariatric surgery, 74 with the advantage that medications can be paused or stopped and have no inherent surgical risks.…”

Section: Discussionmentioning

confidence: 99%

Potent incretin‐based therapy for obesity: A systematic review and meta‐analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety

Müllertz,

Sandsdal,

Jensen

et al. 2024

Obesity Reviews

View full text Add to dashboard Cite

SummaryPotent incretin‐based therapy shows promise for the treatment of obesity along with reduced incidence of cardiovascular events in patients with preexisting cardiovascular disease and obesity. This study assessed the efficacy and safety of the incretin‐based obesity treatments, once‐weekly subcutaneous semaglutide 2.4 mg and tirzepatide 10 or 15 mg, in people with obesity without diabetes. Of the 744 records identified, seven randomized controlled trials (n = 5140) were included. Five studies (n = 3288) investigated semaglutide and two studies (n = 1852) investigated tirzepatide. The treatment effect, shown as placebo‐subtracted difference, on body weight was −15.0% (95% CI, −17.8 to −12.2) with −12.9% (95% CI, −14.7 to −11.1) for semaglutide and −19.2% (95% CI, −22.2 to −16.2) for tirzepatide. The treatment effect on waist circumference was −11.4 cm (95% CI, −13.7 to −9.2) with −9.7 cm (95% CI, −10.8 to −8.5) for semaglutide and −14.6 cm (95% CI, −15.8 to −13.4) for tirzepatide. The adverse events related to semaglutide and tirzepatide were primarily of mild‐to‐moderate severity and mostly gastrointestinal, which was more frequent during the dose‐titration period and leveled off during the treatment period. This emphasizes that once‐weekly subcutaneous semaglutide 2.4 mg and tirzepatide 10 or 15 mg induce large reductions in body weight and waist circumference and are generally well‐tolerated.

show abstract

Section: Discussionmentioning

confidence: 99%

Potent incretin‐based therapy for obesity: A systematic review and meta‐analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety

Müllertz,

Sandsdal,

Jensen

et al. 2024

Obesity Reviews

View full text Add to dashboard Cite

show abstract

“…A recently published paper showed that 68 weeks of use of a very high dose of oral semaglutide, 50 mg/day, was associated with 15.1% weight loss from the baseline, with 80% of patients reporting gastrointestinal side effects. 23 Danuglipron is another small molecule oral GLP1RA that has reached the stage of phase-3 clinical trials in diabetes and obesity. 24 Although orforglipron has weight loss data that is less impressive than injectable tirzepatide and injectable retatrutide, it has a major advantage of being an oral and not injectable medication with less gastrointestinal side effects based on the hazard ratio values.…”

Section: Discussionmentioning

confidence: 99%

Orforglipron, a novel non‐peptide oral daily glucagon‐like peptide‐1 receptor agonist as an anti‐obesity medicine: A systematic review and meta‐analysis

Dutta,

Nagendra,

Anne

et al. 2024

Obesity Science & Practice

View full text Add to dashboard Cite

BackgroundOrforglipron is a novel once‐daily oral non‐peptide glucagon‐like peptide‐1 receptor agonist with several recently published randomized controlled trials (RCTs) evaluating its role in diabetes and obesity. No meta‐analysis has analyzed the efficacy and safety of orforglipron; this meta‐analysis aimed to address this knowledge gap.MethodsA systematic search was conducted in electronic databases to identify RCTs that included individuals with obesity who were administered orforglipron and compared to either a placebo or an active comparator. The primary outcome of interest was the percent change in body weight.ResultsFrom 12 initially screened articles, data from three RCTs involving 774 people were analyzed with a follow‐up duration of up to 36 weeks. Compared to placebo, patients receiving orforglipron 12 mg/day (mean difference (MD), MD −5.48%, 95% CI [−7.64, −3.33], p < 0.01), 24 mg/day (MD −8.51%, 95% confidence interval (CI) [−9.88, −7.14], p < 0.01), 36 mg/day (MD −8.84%, 95% CI [−11.68, −6.00], p < 0.01) and 45 mg/day (MD −8.24%, 95% CI [−12.84, −3.63], p < 0.01) had a significantly greater percent reduction in body weight. The percentage of patients being able to achieve >15% weight loss from baseline was significantly higher with orforglipron 24 mg/day [Odds ratio (OR) 21.90 (95% CI [4.06, 118.15], p = 0.0003), 36 mg/day (OR 17.43, 95% CI [3.18, 95.66], p = 0.001) and 45 mg/day (OR 23.17, 95% CI [4.37, 123.03], p = 0.0002). Total but not severe adverse events were significantly higher with all the doses of orforglipron compared to placebo, with the hazard ratios being higher with higher doses. Gastrointestinal side‐effects were predominant side effects, being dose‐dependent, with nausea, vomiting, constipation, and gastroesophageal reflux being the predominant ones.ConclusionOrforglipron at 24–45 mg/day doses is an effective weight loss medication. The efficacy versus side effect profile suggests that 24–36 mg/day is the most optimal dose for orforglipron as an anti‐obesity medicine.

show abstract

“…A number of agents are under study, 13 including the amylin receptor agonist, cagrilintide, combined with the GLP‐1RA semaglutide, 14 survodutide, a glucagon/GLP‐1 receptor dual agonist, 15 and retatrutide, 16 a single peptide with agonist activity at the GIP, GLP‐1, and glucagon receptors. Oral agents being developed include orforglipron, a nonpeptide GLP‐1 receptor agonist, 17 and high‐dose oral semaglutide 18 . Maridebart cafraglutide is being developed as a monthly injection, acting as a GLP‐1 RA and an antagonist of the GIP receptor 19 .…”

Section: Agent Brand Name Administration Manufacturer % Weight Lossa ...mentioning

confidence: 99%

The 2023 WCIRDC: Obesity

Bloomgarden

2024

Journal of Diabetes

View full text Add to dashboard Cite

Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial

Cited by 129 publications

References 33 publications

Potent incretin‐based therapy for obesity: A systematic review and meta‐analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety

Potent incretin‐based therapy for obesity: A systematic review and meta‐analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety

Orforglipron, a novel non‐peptide oral daily glucagon‐like peptide‐1 receptor agonist as an anti‐obesity medicine: A systematic review and meta‐analysis

The 2023 WCIRDC: Obesity

Contact Info

Product

Resources

About